Suh Yousin, Vijg Jan
Department of Molecular Medicine and Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas 78425, USA.
Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):559-71. doi: 10.1089/ars.2006.8.559.
Aging of somatic cells can be defined as the gradual loss of the information embedded in the global and local properties of complex macromolecular networks. This loss of information may reflect the dynamic interplay between stochastic factors, such as the accumulation of unrepaired somatic damage, and gene-encoded programmatic responses. This would ultimately result in loss of function, impaired response to environmental challenge, and a progressively increased incidence of disease. Here the authors present the case for aging as a continuous battle between maintaining genomic integrity and ensuring sufficient cell functional mass. Focusing on aging of the liver in rodents, evidence is presented that normal aging is associated with a gradual accumulation of random alterations in the DNA of the genome as a consequence of imperfect DNA repair and a decrease in the rate of DNA damage-induced apoptosis. Apoptosis is the cell's genome maintenance mechanism of last resort and an imbalance towards apoptosis can contribute to manifestations of aging-related phenotypes, as exemplified by mouse models of premature aging due to genetic defects in genome maintenance. Prospects to reset the clock in this zero sum game between survival and the maintenance of phenotypic integrity will be discussed.
体细胞衰老可定义为复杂大分子网络全局和局部特性中所嵌入信息的逐渐丧失。这种信息丧失可能反映了随机因素（如未修复的体细胞损伤积累）与基因编码的程序性反应之间的动态相互作用。这最终会导致功能丧失、对环境挑战的反应受损以及疾病发病率的逐渐上升。在此，作者提出衰老乃维持基因组完整性与确保足够细胞功能量之间持续斗争的观点。以啮齿动物肝脏衰老为例，有证据表明正常衰老与基因组DNA因DNA修复不完善而逐渐积累随机改变以及DNA损伤诱导的凋亡速率降低有关。凋亡是细胞基因组维护的最后手段，而凋亡失衡会导致衰老相关表型的出现，因基因组维护存在遗传缺陷而早衰的小鼠模型就是例证。本文将讨论在生存与维持表型完整性这场零和博弈中重置时钟的前景。
